1. Field of the Invention
The present invention relates to the field of ultrasound contrast agents.
2. Description of the Background Art
Physicians and physiologists have long recognized the significance of local perfusion in the assessment of wound healing, diabetes, viability of transplanted organs and reattached limbs, the diagnosis of cancerous lesions and the assessment of myocardial function, however to date there is no method that can provide a direct assessment. It has been clear that fundamental changes in tissue perfusion are involved in disease progression, or in some cases in the onset of a disease state. Many imaging techniques have been developed to indirectly detect ischemia, for example ultrasonic and magnetic resonance schemes that evaluate the extent and quality of the regional motion of the beating heart. An opportunity is presented by contrast-assisted ultrasonic imaging with second and third generation agents and new imaging strategies, since the echoes from blood are now far stronger, and local bubble destruction may allow us to map microvascular transit time on a far smaller scale. In addition, we may have the ability to remotely manipulate agents within the body using radiation force. Contrast-assisted imaging is also less expensive than alternative vascular imaging techniques.
Contrast-assisted imaging methods have failed to produce the expected results for reasons that include the lack if fundamental understanding of the interaction between ultrasound and the microbubbles, and difficulties associated with some of the artifacts that can arise. In cardiology, the use of the returned signal amplitude has been particularly difficult since the contrast agent can also attenuate the signal and therefore make interpretation of amplitude fluctuations difficult.
Cancer currently accounts for 15.8% of the deaths within the United States. Although malignant breast masses can often be differentiated using ultrasound due to an increase in the attenuation and decrease in the backscattered echo, these changes are absent in approximately 10% of malignant masses.
More than 60 million people in the United States have some form of cardiovascular disease, with CVD playing a major role in more than 954,000 deaths annually. This is more than 42 percent of the deaths in the United States each year. Ultrasound remains the premier imaging modality for the detection and valuation of CVD, however the current inability of ultrasound to map flow within the coronary arteries, or to map myocardial perfusion is a significant limitation. Ultrasound contrast imaging shows the potential to address these current limitations but needs improved signal processing with definitive detection of bubbles to improve clinical acceptance.
While ultrasonic contrast agents were first considered in 1968, the development of agents with extended persistence provides exciting new opportunities to image the microvasculature. In the past few years, microbubbles have been developed that can survive within the circulation for extended periods. New agents include high molecular weight gases that have a low diffusion constant and have been incorporated into lipid or albumin shells. Agents under development include substances that are intended to adhere to particular tissues and improve the detection of plaque or tumor vasculature.
Also, while contrast agents have been used to increase the amplitude of scatter since 1970, techniques to differentiate bubble and tissue echoes have been proposed very recently. The scattering and attenuation properties of certain contrast agents have been studied. Experiments have shown the nonlinear increase in scattered echoes and the change in harmonic signal content with transmitted pressure. Use of harmonic imaging in vitro has been demonstrated and has provided evidence that cross correlation can be used to track microbubbles. Use of 5 MHz transmission and 2.5 MHz subharmonic reception has been evaluated, demonstrating that subharmonic peaks from the contrast agent Albunex(copyright) can be detected in vitro. Studies of attenuation and transmission have shown the high attenuation of acoustic contrast agents, a significant factor in cardiac imaging. New agents have been presented in many recent conference abstracts.
Clinical evaluation of current contrast-assisted imaging techniques have shown that artifacts can reduce the effectiveness of estimations of myocardial perfusion. Specifically, attenuation and rib artifacts are problematic for operating modes which base the perfusion estimate on the video intensity of the returned signal to map perfusion. Concerns about safety have been reported in, particularly for high intensities and low frequencies ( less than 2 MHz). There remains the need in the art for improved ultrasound techniques.
In accordance with the present invention, a method of identifying gaseous bubbles in a liquid comprises introducing an ultrasound contrast agent into the liquid so as to form gaseous bubbles in the liquid. A first ultrasound pulse centered at a first frequency is directed onto the bubbles, so as to cause the bubbles to undergo a first oscillating size change and produce a corresponding first oscillating echo signal. The first oscillating echo signal produced by the bubbles is detected, and the bubbles are identified based upon the detected first echo signal.